Antipsychotics (Atypical)
Level |
Direction |
Primary Outcome |
Patient/Process |
Setting |
Reference |
I
|
Supportive (Green)
|
Level of agitation
|
Patient
|
In-Patient
|
Breier A., Meehan K., Birkett M., et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry 2002; 59(5):441-8. Medline
|
I
|
Supportive (Green)
|
Time to sedation
|
Patient
|
ED-MD
|
Chan EW., Taylor DM., Knott JC., Phillips GA., Castle DJ., Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med 2013; 61(1):72-81. Medline
|
I
|
Supportive (Green)
|
Reduction in (PANSS-EC) scale over 120 minutes
|
Process
|
ED-MD
|
Currier GW., et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65(3):386-94. Medline
|
I
|
Supportive (Green)
|
Decrease in acute psychotic agitation
|
Patient
|
In-Patient
|
Katagiri H., Fujikoshi S., Suzuki T., et al. A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in japanese patients for schizophrenia with acute agitation. BMC Psychiatry 2013; 13:20-244X-13-20. Medline
|
I
|
Supportive (Green)
|
Reduction in agitation at 1h
|
Patient
|
In-Patient
|
Kinon BJ., Ahl J., Rotelli MD., McMullen E. Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia. Am J Emerg Med 2004; 22(3):181-6. Medline
|
I
|
Supportive (Green)
|
Reduction in agitation at 2 hours and 24 hours
|
Patient
|
In-Patient
|
Meehan K., Zhang F., David S., et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001; 21(4):389-97. Medline
|
I
|
Supportive (Green)
|
PANSS Excited Component scale
|
Patient
|
In-Patient
|
Meehan KM., Wang H., David SR., Nisivoccia JR., et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 2002; 26(4):494-504. Medline
|
I
|
Supportive (Green)
|
Mean change in the Positive and Negative Syndrome Scale-Excited Component (PEC) from baseline to 2 hours post-dose
|
Patient
|
In-Patient
|
Tran-Johnson TK., Sack DA., Marcus RN., Auby P., McQuade RD., Oren DA. Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: A randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2007; 68(1):111-119. Medline
|
I
|
Supportive (Green)
|
Control of agitation
|
Patient
|
ED-MD
|
Yildiz A., Sachs GS., Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003; 20:339-46. Medline
|
I
|
Neutral (Yellow)
|
Efficacy
|
Patient
|
In-Patient
|
Tulloch KJ., Zed PJ. Intramuscular olanzapine in the management of acute agitation. Ann Pharmacother 2004; 38(12):2128-2135. Medline
|
II
|
Supportive (Green)
|
Sedation
|
Patient
|
ED-MD
|
Korczak V, Kirby A, Gunja N. Chemical agents for the sedation of agitated patients in the ED: a systematic review. Am J Emerg Med 2016; 34(12):2426-31. Medline
|
II
|
Supportive (Green)
|
Prolongation/lengthening QTc
|
Patient
|
In-Patient
|
Lindborg SR., Beasley CM., Alaka K., Taylor CC. Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients. Psychiatry Res 2003; 119(1-2):113-23. Medline
|
II
|
Supportive (Green)
|
Additional medication intervention
|
Patient
|
ED-MD
|
MacDonald K., Wilson M., Minassian A., et al. A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation. J Clin Psychopharmacol 2012; 32(3):317-22. Medline
|
II
|
Supportive (Green)
|
Change from baseline on the PANSS-EC score
|
Patient
|
ED-MD
|
Suzuki H., Gen K., Takahashi Y. A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia. Hum Psychopharmacol 2014; 29(1):83-88. Medline
|
III
|
Supportive (Green)
|
Overt Agitation Severity Scale
|
Process
|
ED-MD
|
Baldacara L., Sanches M., Cordeiro DC., Jackoswski AP. Rapid tranquilization for agitated patients in emergency psychiatric rooms: A randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Rev Bras Psiquiatr 2011; 33(1):30-9. Medline
|
III
|
Supportive (Green)
|
Positive and Negative Syndrome
Scale (PANSS-EC)
|
Patient
|
ED-MD
|
Centorrino F., Meyers AL., Ahl J., et al. An observational study of the effectiveness and safety of intramuscular olanzapine in the treatment of acute agitation in patients with bipolar mania or schizophrenia/schizoaffective disorder. Hum Psychopharmacol 2007; 22(7):455-62. Medline
|
III
|
Supportive (Green)
|
Agitation level
|
Patient
|
ED-MD
|
San L., Arranz B., Querejeta I., Barrio S., De la Gandara J., Perez V. A naturalistic multicenter study of intramuscular olanzapine in the treatment of acutely agitated manic or schizophrenic patients. Eur Psychiatry 2006; 21(8):539-43. Medline
|
III
|
Supportive (Green)
|
Reduction on agitation scale at 30 min
|
Patient
|
ED-MD
|
Veser FH., Veser BD., McMullan JT., Zealberg J., Currier GW. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12(2):103-108. Medline
|
III
|
Neutral (Yellow)
|
Agitation-Calmness Evaluation Scale
|
Patient
|
ED-MD
|
Battaglia J., Lindborg SR., Alaka K., Meehan K., Wright P. Calming versus sedative effects of intramuscular olanzapine in agitated patients. Am J Emerg Med 2003; 21(3):192-8. Medline
|
Antipsychotics (Typical)
Level |
Direction |
Primary Outcome |
Patient/Process |
Setting |
Reference |
I
|
Supportive (Green)
|
Reduction in agitation
|
Patient
|
In-Patient
|
Alexander J., Tharyan P., Adams C., John T., Mol C., Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry 2004; 185:63-9. Medline
|
I
|
Supportive (Green)
|
Symptom reduction
|
Patient
|
ED-MD
|
Battaglia J., Moss S., Rush J., et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter prospective double-blind, emergency department study. Am J Emerg Med 1997; 15:335-40. Medline
|
I
|
Supportive (Green)
|
Relief of shortness of breath
|
Patient
|
In-Patient
|
Bieniek S., Ownby RL., et al. A Double-Blind Study of Lorazepam versus the Combination of Haloperidol and Lorazepam in Managing Agitation. Pharmacotherapy 1998; 18(1):57-62. Medline
|
I
|
Supportive (Green)
|
Level of agitation
|
Patient
|
In-Patient
|
Breier A., Meehan K., Birkett M., et al. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry 2002; 59(5):441-8. Medline
|
I
|
Supportive (Green)
|
Reduction of manic symptoms within two hours
|
Patient
|
ED-MD
|
Chouinard G., Annable L., Turnier L., et al. A double-blind randomized clinical trial of rapid tranquilization with I.M. clonazepam and I.M. haloperidol in agitated psychotic patients with manic symptoms. Can J Psychiatry 1993; 38 (S4):S114-21. Medline
|
I
|
Supportive (Green)
|
Reduction in (PANSS-EC) scale over 120 minutes
|
Process
|
ED-MD
|
Currier GW., et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65(3):386-94. Medline
|
I
|
Supportive (Green)
|
Adequate sedation
|
Patient
|
Other
|
deSouza IS, Thode HC Jr, Shrestha P, Allen R, Koos J, Singer AJ. Rapid tranquilization of the agitated patient in the emergency department: A systematic review and network meta-analysis. Am J Emerg Med 2022; 51:363–73. Medline
|
I
|
Supportive (Green)
|
Symptom reduction
|
Patient
|
ED-MD
|
Foster S., Kessel J., Berman ME., et al. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Internat Clinical Psychopharm 1997; 12:175-9. Medline
|
I
|
Supportive (Green)
|
Sedation at 5 min
|
Patient
|
ED-MD
|
Knott JC., Taylor DM., Castle DJ. Randomized Clinical Trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. CJEM 2006; 47(11):61-7. Medline
|
I
|
Supportive (Green)
|
Proportion of patients with AMSS 0 or lower at 15 minutes
|
Patient
|
ED-MD
|
Martel ML, Driver BE, Miner JR, Biros MH, Cole JB. Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Acad Emerg Med 2021; 28(4):421-34. Medline
|
I
|
Supportive (Green)
|
Time to sedation
|
Process
|
ED-MD
|
Nobay F., Simon BC., Levitt MA., Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med 2004; 11(7):744-9. Medline
|
I
|
Supportive (Green)
|
Tranquilization
|
Patient
|
ED-MD
|
Powney MJ., Adams CE., Jones H. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev 2012; 11:CD009377. Medline
|
I
|
Supportive (Green)
|
Tranquil or asleep at 15 min
|
Patient
|
ED-MD
|
Raveendran NS., Tharyan P., Alexander J., Adams CE., TREC-India II Collaborative Group. Rapid tranquillisation in psychiatric emergency settings in india: Pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine. BMJ 2007; 335(7625):865. Medline
|
I
|
Supportive (Green)
|
Brief Psychiatric Rating Scale score
|
Patient
|
ED-MD
|
Resnick M., Burton BT. Droperidol vs. haloperidol in the initial management of acutely agitated patients. J Clin Psychiatry 1984; 45(7):298-9. Medline
|
I
|
Supportive (Green)
|
Sedation
|
Patient
|
PH-Paramedic
|
Richards JR., Derlet RW., Duncan DR., et al. Chemical restraint for the agitated patient in the emergency department: Lorazepam versus droperidol. J Emerg Med 1998; 16:567-73. Medline
|
I
|
Supportive (Green)
|
Five point combativeness scale
|
Patient
|
ED-MD
|
Thomas H., Schwartz E., Petrilli R. Droperidol versus haloperidol for chemical restraint of agitated and combative patients. Ann Emerg Med 1992; 21(4):78-84. Medline
|
I
|
Supportive (Green)
|
Safety
|
Patient
|
PH-Bystander
|
TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003; 327(7417):708–713. Medline
|
I
|
Supportive (Green)
|
Control of agitation
|
Patient
|
ED-MD
|
Yildiz A., Sachs GS., Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003; 20:339-46. Medline
|
I
|
Neutral (Yellow)
|
Time to sedation
|
Patient
|
ED-MD
|
Chan EW., Taylor DM., Knott JC., Phillips GA., Castle DJ., Kong DC. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med 2013; 61(1):72-81. Medline
|
I
|
Neutral (Yellow)
|
Decrease in symptoms
|
Patient
|
In-Patient
|
Lonergan E., Luxenberg J., Colford J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2001; (4):CD002852. Medline
|
I
|
Neutral (Yellow)
|
Reversal of hypoglycemic episode
|
Patient
|
PH-Paramedic
|
Martel M., Sterzinger A., Miner J., et al. Management of acute undifferentiated agitation in the emergency department: A randomized double blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005; 12(12)1167-72. Medline
|
I
|
Neutral (Yellow)
|
Motor agitation
|
Patient
|
In-Patient
|
Wyant M., Diamond BI., et al. The Use of Midazolam in Acutely Agitated Psychiatric Patients. Psychopharmacology Bulletin 1990; 26(1):126-129. Medline
|
II
|
Supportive (Green)
|
Efficacy
|
Process
|
PH-Paramedic & CCT
|
Brown N, Edwards T, McIntyre I, Faulkner M. A retrospective cohort study of pre-hospital agitation management by advanced paramedic practitioners in critical care. Br Paramed J Dec 2022; 7(3):8-14. Medline
|
II
|
Supportive (Green)
|
Tolerability, Reduction in agitation (PANSS)
|
Process
|
ED-MD
|
Currier GW., Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001; 62(3):153-7. Medline
|
II
|
Supportive (Green)
|
Sedation
|
Patient
|
ED-MD
|
Korczak V, Kirby A, Gunja N. Chemical agents for the sedation of agitated patients in the ED: a systematic review. Am J Emerg Med 2016; 34(12):2426-31. Medline
|
II
|
Supportive (Green)
|
Complications
|
Process
|
In-Patient
|
O'Connor L., Rebesco M., Robinson C., Gross K., Castellana A., O'Connor MJ., et al. Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only. PEC 2018 1-9. Medline
|
II
|
Supportive (Green)
|
Change from baseline on the PANSS-EC score
|
Patient
|
ED-MD
|
Suzuki H., Gen K., Takahashi Y. A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia. Hum Psychopharmacol 2014; 29(1):83-88. Medline
|
II
|
Supportive (Green)
|
Time to adequate sedation
|
Patient
|
ED-MD
|
Thiemann P, Roy D, Huecker M, Senn J, Javed J, Thomas A, Shaw I. Prospective study of haloperidol plus lorazepam versus droperidol plus midazolam for the treatment of acute agitation in the emergency department. Am J Emerg Med 2022; 55: 76–81. Medline
|
II
|
Neutral (Yellow)
|
Prolongation/lengthening QTc
|
Patient
|
In-Patient
|
Lindborg SR., Beasley CM., Alaka K., Taylor CC. Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients. Psychiatry Res 2003; 119(1-2):113-23. Medline
|
II
|
Neutral (Yellow)
|
Additional medication intervention
|
Patient
|
ED-MD
|
MacDonald K., Wilson M., Minassian A., et al. A naturalistic study of intramuscular haloperidol versus intramuscular olanzapine for the management of acute agitation. J Clin Psychopharmacol 2012; 32(3):317-22. Medline
|
II
|
Neutral (Yellow)
|
Need for additional interventions
|
Patient
|
PH-Paramedic
|
Martel M., Miner J., Fringer R., Sufka K., Miamen A., Ho J., Clinton J., Michelle B. Discontinuation of Droperidol for the Control of Acutely Agitated Out-of-Hospital Patients. PEC 2005; 9(1):44-8. Medline
|
III
|
Supportive (Green)
|
Overt Agitation Severity Scale
|
Process
|
ED-MD
|
Baldacara L., Sanches M., Cordeiro DC., Jackoswski AP. Rapid tranquilization for agitated patients in emergency psychiatric rooms: A randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Rev Bras Psiquiatr 2011; 33(1):30-9. Medline
|
III
|
Supportive (Green)
|
Sedation
|
Patient
|
ED-MD
|
Clinton JE., Sterner S., Stelmachers Z., et al. Haloperidol for sedation of disruptive emergency patients. Ann Emerg Med 1987; 16:319-22. Medline
|
III
|
Supportive (Green)
|
5 min post-drug agitation
|
Patient
|
PH-Paramedic
|
Hick JL., Mahoney BD., Lappe M. Prehospital sedation with intramuscular droperidol: a one-year pilot. Prehosp Emerg Care 2001; 5(4):391-4. Medline
|
III
|
Supportive (Green)
|
Time to sedation
|
Patient
|
ED-MD
|
Huf G., Coutinho ES., Adams CE., TREC Collaborative Group. Rapid tranquillisation in psychiatric emergency settings in brazil: Pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine. BMJ 2007; 335(7625):869. Medline
|
III
|
Supportive (Green)
|
Effectiveness and safety
|
Patient
|
Other
|
Ramsden SC, Pergjika A, Janssen AC, Mudahar S, Fawcett A, Walkup JT, Hoffmann JA. A systematic review of the effectiveness and safety of droperidol for pediatric agitation in acute care settings. Acad Emerg Med 2022. Medline
|
III
|
Supportive (Green)
|
Agitation level
|
Patient
|
PH-Paramedic
|
Rosen CL., Ratliff AF., Wolfe RE., et al. The efficacy of intravenous droperidol in the prehospital setting. J Emerg Med 1997; 15(1):13-7. Medline
|
III
|
Supportive (Green)
|
Symptom Profile Score
|
Patient
|
ED-MD
|
Stotsky BA. Relative efficacy of parenteral haloperidol and thiothixene for the emergency treatment of acutely excited and agitated patients. Dis Nerv Syst 1977; 38(12):967-973. Medline
|
III
|
Supportive (Green)
|
Reduction on agitation scale at 30 min
|
Patient
|
ED-MD
|
Veser FH., Veser BD., McMullan JT., Zealberg J., Currier GW. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12(2):103-108. Medline
|
III
|
Neutral (Yellow)
|
Number of patients with adverse events
|
Patient
|
PH-Paramedic
|
Page CB, Parker LE, Rashford SJ, Isoardi KZ, Isbister GK. A Prospective Study of the Safety and Effectiveness of Droperidol in Children for Prehospital Acute Behavioural Disturbance. Prehospital emergency care: official journal of the National Association of EMS Physicians and the National Association of State EMS Directors 2018:1-26. Medline
|
III
|
Opposes (Red)
|
Adverse Event
|
Patient
|
ED-MD
|
Palombaro J., Klingelberger CE. Angioedema associated with Droperidol administration. Ann Emerg Med 1996; 27:379-81. Medline
|
Benzodiazepines
Level |
Direction |
Primary Outcome |
Patient/Process |
Setting |
Reference |
I
|
Supportive (Green)
|
Reduction in agitation
|
Patient
|
In-Patient
|
Alexander J., Tharyan P., Adams C., John T., Mol C., Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry 2004; 185:63-9. Medline
|
I
|
Supportive (Green)
|
Symptom reduction
|
Patient
|
ED-MD
|
Battaglia J., Moss S., Rush J., et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter prospective double-blind, emergency department study. Am J Emerg Med 1997; 15:335-40. Medline
|
I
|
Supportive (Green)
|
Resolution of symptoms
|
Patient
|
ED-MD
|
Bieniek S., Ownby RL., et al. A Double-Blind Study of Lorazepam versus the Combination of Haloperidol and Lorazepam in Managing Agitation. Pharmacotherapy 1998; 18(1):57-62. Medline
|
I
|
Supportive (Green)
|
Reduction of manic symptoms within two hours
|
Patient
|
ED-MD
|
Chouinard G., Annable L., Turnier L., et al. A double-blind randomized clinical trial of rapid tranquilization with I.M. clonazepam and I.M. haloperidol in agitated psychotic patients with manic symptoms. Can J Psychiatry 1993; 38 (S4):S114-21. Medline
|
I
|
Supportive (Green)
|
Reduction in (PANSS-EC) scale over 120 minutes
|
Process
|
ED-MD
|
Currier GW., et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65(3):386-94. Medline
|
I
|
Supportive (Green)
|
Symptom reduction
|
Patient
|
ED-MD
|
Foster S., Kessel J., Berman ME., et al. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Internat Clinical Psychopharm 1997; 12:175-9. Medline
|
I
|
Supportive (Green)
|
Reduction in agitation at 1h
|
Patient
|
In-Patient
|
Kinon BJ., Ahl J., Rotelli MD., McMullen E. Efficacy of accelerated dose titration of olanzapine with adjunctive lorazepam to treat acute agitation in schizophrenia. Am J Emerg Med 2004; 22(3):181-6. Medline
|
I
|
Supportive (Green)
|
Sedation at 5 min
|
Patient
|
ED-MD
|
Knott JC., Taylor DM., Castle DJ. Randomized Clinical Trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. CJEM 2006; 47(11):61-7. Medline
|
I
|
Supportive (Green)
|
Sedation
|
Patient
|
ED-MD
|
Martel M., Sterzinger A., Miner J., et al. Management of acute undifferentiated agitation in the emergency department: A randomized double blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005; 12(12)1167-72. Medline
|
I
|
Supportive (Green)
|
PANSS Excited Component scale
|
Patient
|
In-Patient
|
Meehan KM., Wang H., David SR., Nisivoccia JR., et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 2002; 26(4):494-504. Medline
|
I
|
Supportive (Green)
|
Time to sedation
|
Process
|
ED-MD
|
Nobay F., Simon BC., Levitt MA., Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med 2004; 11(7):744-9. Medline
|
I
|
Supportive (Green)
|
Sedation
|
Patient
|
PH-Paramedic
|
Richards JR., Derlet RW., Duncan DR., et al. Chemical restraint for the agitated patient in the emergency department: Lorazepam versus droperidol. J Emerg Med 1998; 16:567-73. Medline
|
I
|
Supportive (Green)
|
Patients tranquil or sedated at 20 mins
|
Patient
|
ED-MD
|
TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003; 327(7417):708–713. Medline
|
I
|
Supportive (Green)
|
Motor agitation
|
Patient
|
In-Patient
|
Wyant M., Diamond BI., et al. The Use of Midazolam in Acutely Agitated Psychiatric Patients. Psychopharmacology Bulletin 1990; 26(1):126-129. Medline
|
I
|
Supportive (Green)
|
Control of agitation
|
Patient
|
ED-MD
|
Yildiz A., Sachs GS., Turgay A. Pharmacological management of agitation in emergency settings. Emerg Med J 2003; 20:339-46. Medline
|
I
|
Neutral (Yellow)
|
Adequate sedation within 30 mins.
|
Patient
|
Other
|
deSouza IS, Thode HC Jr, Shrestha P, Allen R, Koos J, Singer AJ. Rapid tranquilization of the agitated patient in the emergency department: A systematic review and network meta-analysis. Am J Emerg Med 2022; 51:363–73. Medline
|
I
|
Neutral (Yellow)
|
Global impression - no improvement, sedation or need for additional medication
|
Patient
|
In-Patient
|
Gillies D., Sampson S., Beck A., Rathbone J. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev 2013; 4. Medline
|
I
|
Neutral (Yellow)
|
Sedation at 15 minutes
|
Patient
|
ED-MD
|
Martel ML, Driver BE, Miner JR, Biros MH, Cole JB. Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department. Acad Emerg Med 2021; 28(4):421-34. Medline
|
I
|
Neutral (Yellow)
|
Reduction in agitation at 2 hours and 24 hours
|
Patient
|
In-Patient
|
Meehan K., Zhang F., David S., et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001; 21(4):389-97. Medline
|
II
|
Supportive (Green)
|
Efficacy
|
Process
|
PH-Paramedic & CCT
|
Brown N, Edwards T, McIntyre I, Faulkner M. A retrospective cohort study of pre-hospital agitation management by advanced paramedic practitioners in critical care. Br Paramed J Dec 2022; 7(3):8-14. Medline
|
II
|
Supportive (Green)
|
Tolerability, Reduction in agitation (PANSS)
|
Process
|
ED-MD
|
Currier GW., Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001; 62(3):153-7. Medline
|
II
|
Supportive (Green)
|
Sedation
|
Patient
|
ED-MD
|
Korczak V, Kirby A, Gunja N. Chemical agents for the sedation of agitated patients in the ED: a systematic review. Am J Emerg Med 2016; 34(12):2426-31. Medline
|
II
|
Supportive (Green)
|
Improvement
|
Patient
|
PH-Paramedic
|
Sandoval S, Goyal A, Frawley J, et al. Prehospital Use of Ketamine versus Benzodiazepines for Sedation among Pediatric Patients with Behavioral Emergencies. Prehosp Emerg Care 2023;1-7. Medline
|
II
|
Opposes (Red)
|
Need for additional interventions
|
Patient
|
PH-Paramedic
|
Martel M., Miner J., Fringer R., Sufka K., Miamen A., Ho J., Clinton J., Michelle B. Discontinuation of Droperidol for the Control of Acutely Agitated Out-of-Hospital Patients. PEC 2005; 9(1):44-8. Medline
|
III
|
Supportive (Green)
|
Reduction on agitation scale at 30 min
|
Patient
|
ED-MD
|
Veser FH., Veser BD., McMullan JT., Zealberg J., Currier GW. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: A pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12(2):103-108. Medline
|
X
|
Not Yet Graded (White)
|
-
|
|
|
Muldowney M, Counts CR, Maider MC, Sharar SR, et al. A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting. Ann Emerg Med 2024. Medline
|
Ketamine
Level |
Direction |
Primary Outcome |
Patient/Process |
Setting |
Reference |
I
|
Supportive (Green)
|
Time to sedation
|
Patient
|
Other
|
deSouza IS, Thode HC Jr, Shrestha P, Allen R, Koos J, Singer AJ. Rapid tranquilization of the agitated patient in the emergency department: A systematic review and network meta-analysis. Am J Emerg Med 2022; 51:363–73. Medline
|
I
|
Opposes (Red)
|
Need for intubation
|
Process
|
PH-Paramedic
|
Lipscombe C, Akhlaghi H, Groombridge C, Bernard S, Smith K, Olaussen A. Intubation Rates following Prehospital Administration of Ketamine for Acute Agitation: A Systematic Review and Meta-Analysis. Prehosp Emerg Care 2022; 1–15. Medline
|
II
|
Supportive (Green)
|
Incidence of intubation after prehospital ketamine use
|
Process
|
PH-Paramedic
|
Coffey SK, Vakkalanka JP, Egan H, Wallace K, Harland KK, Mohr NM, et al. Outcomes Associated with Lower Doses of Ketamine by Emergency Medical Services for Profound Agitation. West J Emerg Med 2021; 22(5):1183–9. Medline
|
II
|
Supportive (Green)
|
Intubation post ketamine
|
Patient
|
PH-Paramedic
|
Cunningham C, Gross K, Broach JP, O’Connor L. Patient Outcomes Following Ketamine Administration for Acute Agitation with a Decreased Dosing Protocol in the Prehospital Setting. Prehosp Disaster Med 2021; 36(3)276–82. Medline
|
II
|
Supportive (Green)
|
Adequate sedation.
|
Patient
|
PH-Paramedic & MD
|
Cunningham C, Gross K, Broach JP, O'Connor L. Patient Outcomes Following Ketamine Administration for Acute Agitation with a Decreased Dosing Protocol in the Prehospital Setting. Prehosp Disaster Med 2021:1-7. Medline
|
II
|
Supportive (Green)
|
Safety
|
Patient
|
PH-Paramedic
|
Goyal A, Frawley J, Gappy R, Sandoval S, Chen NW, Crowe R, Swor R. Prehospital Ketamine Use in Pediatrics. Prehosp Emerg Care 2022; 1–11 Medline
|
II
|
Supportive (Green)
|
Admission to
an inpatient psychiatry service
|
Process
|
PH-Paramedic
|
Lebin JA, Akhavan AR, Hippe DS, Gittinger MH, Pasic J, McCoy AM, et al. Psychiatric Outcomes of Patients With Severe Agitation Following Administration of Prehospital Ketamine. Academic Emergency Medicine 2019; 26(8):889-96. Medline
|
II
|
Supportive (Green)
|
Agitation control
|
Patient
|
ED-MD
|
Lin J, Figuerado Y, Montgomery A, Lee J, Cannis M, Norton VC, et al. Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study. Am J Emerg Med 2021; 44:306–11. Medline
|
II
|
Supportive (Green)
|
Intubation rate
|
Process
|
ED-Paramedic & CCP
|
Parsch CS, Boonstra A, Teubner D, Emmerton W, McKenny B, Ellis DY. Ketamine reduces the need for intubation in patients with acute severe mental illness and agitation requiring transport to definitive care: An observational study. EMA 2017; 29(3):291-6. Medline
|
II
|
Supportive (Green)
|
Agitation
|
Patient
|
ED-MD
|
Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Ketamine as a first-line treatment for severely agitated emergency department patients. Am J Emerg Med 2017; 35(7):1000-4. Medline
|
II
|
Supportive (Green)
|
Improvement
|
Patient
|
PH-Paramedic
|
Sandoval S, Goyal A, Frawley J, et al. Prehospital Use of Ketamine versus Benzodiazepines for Sedation among Pediatric Patients with Behavioral Emergencies. Prehosp Emerg Care 2023;1-7. Medline
|
II
|
Neutral (Yellow)
|
Safety
|
Patient
|
PH-Paramedic & MD
|
Fernandez AR, Bourn SS, Crowe RP, Bronsky ES, Scheppke KA, Antevy P, et al. Out-of-Hospital Ketamine: Indications for Use, Patient Outcomes, and Associated Mortality. Ann Emerg Med 2021; 78(1):123–31. Medline
|
II
|
Neutral (Yellow)
|
Need for airway intervention
|
Patient
|
ED-MD
|
Parks DJ, Alter SM, Shih RD, Solano JJ, Hughes PG, Clayton LM. Rescue Intubation in the Emergency Department After Prehospital Ketamine Administration for Agitation. Prehosp Disaster Med 2020; 35(6):651-5. Medline
|
II
|
Opposes (Red)
|
Rate of intubation
|
Process
|
In-Patient
|
O'Connor L., Rebesco M., Robinson C., Gross K., Castellana A., O'Connor MJ., et al. Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and Benzodiazepine or Physical Restraint Only. PEC 2018 1-9. Medline
|
III
|
Supportive (Green)
|
Total time to adequate sedation in minutes
|
Process
|
PH-Paramedic
|
Cole JB, Klein LR, Nystrom PC, Moore JC, Driver BE, Fryza BJ, et al. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med 2018; 36(5):789-96. Medline
|
III
|
Supportive (Green)
|
Clinician satisfaction
|
Patient
|
ED-MD
|
Kowalenko T., Kereiakes DJ., Gibler WB., et al. Prehospital diagnosis and treatment of acute myocardial infarction: A critical review. Am Heart J 1992; 123(1):181-90.
|
III
|
Supportive (Green)
|
Safety and effectiveness
|
Patient
|
|
Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis. J Emerg Med 2018; 55(5):670-81. Medline
|
III
|
Supportive (Green)
|
Sedation
|
Patient
|
Other
|
Reicher D. High-Dose Ketamine Sedation of an Agitated Patient During Air Medical Transport. Air Med J 2016; 35(2):84-5. Medline
|
III
|
Supportive (Green)
|
Sedation
|
Patient
|
|
Scaggs TR., Glass DM., Hutchcraft MG., Weir WB. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehosp Disaster Med 2016; 31(5):563-9. Medline
|
III
|
Supportive (Green)
|
Sedation
|
Patient
|
PH-Paramedic
|
Scheppke KA., Braghiroli J., Shalaby M., Chait R. Prehospital use of i.m. ketamine for sedation of violent and agitated patients. West J Emerg Med 2014; 15(7):736-41. Medline
|
III
|
Neutral (Yellow)
|
Time to adequate sedation
|
Process
|
PH-Paramedic
|
Bernard S, Roggenkamp R, Delorenzo A, Stephenson M, Smith K. Use of intramuscular ketamine by paramedics in the management of severely agitated patients. Emerg Med Australas 2021. Medline
|
III
|
Neutral (Yellow)
|
Adverse events
|
Patient
|
PH-Paramedic
|
Isoardi KZ, Parker LE, Page CB, Humphreys MA, Harris K, Rashford S, et al. Ketamine as a rescue treatment for severe acute behavioural disturbance: A prospective prehospital study. Emerg Med Australas 2021; 33(4):610–4. Medline
|
III
|
Neutral (Yellow)
|
Adverse events
|
Patient
|
PH-Paramedic
|
O'Brien MC, Kelleran KJ, Burnett SJ, et al. Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation. Am J Emerg Med. July 2024; 81:10-5. Medline
|
X
|
Not Yet Graded (White)
|
-
|
|
|
Muldowney M, Counts CR, Maider MC, Sharar SR, et al. A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting. Ann Emerg Med 2024. Medline
|
X
|
Not Yet Graded (White)
|
-
|
|
|
Nuhoğlu Ç, Solakoğlu GA, Arslan F, Gülsoy ÖF, Döker KO. Can ketamine administration prevent intubation in patients who cannot comply with NIV due to agitation? BMC Emerg Med 2024; 24(1):187. Medline
|